Lactate dehydrogenase (LDH)-deficient mutants of Streptococcus mutans produce less acid from the metabolism of carbohydrates than do wild-type strains of this organism. As a result, they are less cariogenic. When the mutants are implanted in the mouths of laboratory rats, these animals become relatively resistent to infection by naturally occurring strains of S. mutans. Current studies are devoted to extending these findings to determine the ability of LDH-deficient mutants to serve as effector strains in the replacement therapy of dental caries. Three groups of 15 irus monkeys have been infected with an LDH mutant, its parent, or sham infected. At 3-month intervals, the animals will be assessed for the incidence and severity of dental caries, changes in their oral microbiota, and immunological responses to the infecting agent. In a separate study, the ability of an LDH mutant to inhibit colonization of irus monkeys will be assessed. Also, the end products of glucose and sucrose metabolism will be analyzed in chemostat cultures of the mutant to determine the possible production of toxic metabolites. Finally, a genetic system to promote transfer of chromosomal markers in S. mutans will be attempted. The system to be employed involves use of the R15 plasmid from Escherichia coli.